Unprotected receptive anal intercourse is the top ranking sexual risk behavior leading to HIV infection. Although condoms can prevent viral transmission, large numbers of uninfected men and women who have receptive anal sex with HIV-positive men or men of unknown serostatus do not use condoms consistently -either by choice or due to reasons out of their control. For them, rectal microbicides could be a protection alternative. Rectal microbicides need to be not only efficacious against HIV but, equally important, products that people are able and willing to use. This latter issue is generally referred to as "acceptability." This study will assess rectal microbicide acceptability among men who have sex with men (MSM) and women. With MSM, we will undertake an actual trial iusing a microbicide placebo, that is, a product that is inert and presents no safety concerns yet is undistinguishable from a "real" microbicide. With women, we will conduct in-depth acceptability interviews but no actual trial. Focusing on HIV-negative men who have receptive anal intercourse (RAI) using condoms inconsistently or not at all, the primary aims of this study are to (1) determine, through a rectal gel volume escalation trial, the maximum acceptable volume of gel for use during RAI; (2) determine, through a formulation preference trial, which rectal microbicide delivery vehicle (gel or suppository) is preferred for RAI; and (3) assess, through qualitative and quantitative research methods, whether or not there are different attitudes about and intentions to use rectal microbicide gels as opposed to suppositories; and whether or not attitudes and intentions change from before to after the product trial. Focusing on HIV-negative women who engage in anal sex with men using condoms inconsistently or not at all, the secondary aims of this study are to (I) elicit, through qualitative in-depth interviews, the psychological, social, and cultural factors associated with anal sex and (2) assess, through qualitative and quantitative techniques, attitudes, intention to use, and preferences concerning rectal microbicide gels and suppositories. This study will be conducted by a partnership between the H IV Center for Clinical and Behavioral Studies at New York State Psychiatric Institute and Columbia University, in New York City, New York, and the Fenway Communit Health, in Boston, Massachusetts.